Encapsulation and Delivery of Neutrophic Proteins and Hydrophobic Agents Using PMOXA-PDMS-PMOXA Triblock Polymersomes

Published under an ACS AuthorChoice LicensePolymersomes are attractive nanocarriers for hydrophilic and lipophilic drugs; they are more stable than liposomes, tunable, and relatively easy to prepare. The copolymer composition and molar mass are critical features that determine the physicochemical properties of the polymersomes including the rate of drug release. We used the triblockcopolymer, poly(2-methyl-2-oxazoline)-block-poly-(dimethysiloxane)-block-poly(2-methyl-2-oxazoline) (PIVIOXA-PDIVIS-PMOXA), to form amphipathic polymersomes capable of loading proteins and small hydrophobic agents. The selected agents were unstable neurotrophins (nerve growth factor and brain -derived neurotrophic factor), a large protein CD109, and the fluorescent drug curcumin. We prepared, characterized, and tested polymersomes loaded with selected agents in 2D and 3D biological models. Curcumin-loaded and rhodamine-bound PMOXA-PDMS-PMOXA polymersomes were used to visualize them inside cells. NMethyl-D-aspartate receptor (NNIDAR) agonists and antagonists were also covalently attached to the surface of polymersomes for targeting neurons. Labeled and unlabeled polymersomes with or without loaded agents were characterized using dynamic light scattering (DLS), UV-vis fluorescence spectroscopy, and asymmetrical flow field-flow fractionation (AF(4)). Polymersomes were imaged and tested for biological activity in human and murine fibroblasts, murine macrophages, primary murine dorsal root ganglia, and murine hippocampal cultures. Polymersomes were rapidly internalized and there was a clear intracellular co-localization of the fluorescent drug (curcumin) with the fluorescent rhodamine-labeled polymersomes. Polymersomes containing CD109, a glycosylphosphatidylinositol-anchored protein, promoted cell migration in the model of wound healing. Nerve growth factor-loaded polymersomes effectively enhanced neurite outgrowth in dissociated and explanted dorsal root ganglia. Brain -derived neurotrophic factor increased dendritic spine density in serum-deprived hippocampal slice cultures. NMDAR agonist-and antagomst-functionalized polymersomes targeted selectively neurons over filial cells in mixed cultures. Collectively, the study reveals the successful incorporation into polymersomes of biologically active trophic factors and small hydrophilic agents that retain their biological activity in vitro, as demonstrated in selected central and peripheral tissue models.Peer reviewe

Análise tectono-estratigráfica dos fragmentos Apati e Boici da Bacia do Camaquã, RS

Embora a Bacia do Camaquã venha sendo investigada já há bastante tempo, foram raros os trabalhos que abordaram seus fragmentos mais meridionais. Pouco se sabe, por exemplo, sobre a relação esses pacotes sedimentares com as unidades adjacentes bem como da p roveniência sedimentar e seu contexto tectono - estratigráfico. Por essa razão, tais fragmentos têm sido enquadrados em diferentes unidades estratigráficas. Há também desconhecimento acerca da paleogeografia que determinou as possíveis áreas - fonte de sedimen to durante o desenvolvimento desses pacotes pertencentes à Formação Arroio dos Nobres. Este trabalho propõe - se a analisar os modelos deposicionais e eventos tectono - sedimentares da porção sul da Bacia do Camaquã e seu contato com o Complexo Porongos. A in vestigação endereçada aos fragmentos de bacia dos vales Apati e Boici, será conduzida em termos de análise faciológica, proveniência sedimentar, relação estrutural e revisão de dados da bibliografia a fim de se propor um modelo deposicional e enquadramento estratigráfico da Formação Arroio dos Nobres na região do município de Pinheiro Machado . Para o desenvolvimento desse programa investigativo, foram realiza dos , no campo, levantamentos sistemáticos de perfis colunares e respectiva análise de fácies, e deta lhamento composicional e granulométrico de clastos, bem como análise estrutural, também feita por meio de imagens de satélite. Em laboratório , procedeu - se a análise de minerais pesados por meio de microscopia eletrônica de varredura. Da aplicação desses métodos, conclui - se que os fragmentos de estudo, Apati e Boici, são compostos por 28 fácies sedimentares agrupadas em cinco associações de fácies representativas de leques turbidíticos . Quanto ao enquadramento estratigráfico e relação estrutural, os pacotes sedimentares estudados correspondem à Formação Arroio dos Nobres e apresentam - se em contato com o Complexo Porongos por meio de falhas transcorrentes denotadas por afloramentos de cataclasitos. O estudo de proveniência demonstra que os sedimentos que pree ncheram a bacia do Arroio Boici e o fragmento Apati são, predominantemente, oriundos de rochas graníticas do Terreno Pelotas. A ausência de clastos vulcânicos indica que, no momento de formação desses pacotes, o Terreno Pelotas estava com seu nível crustal profundo exposto e as rochas vulcânicas já haviam sido erodidas. Também ocorre contribuição menos significativa de clastos metamórficos, possivelmente derivados do Terreno Tijucas (Complexo Porongos). Isso deveu - se ao fato do Complexo Porongos ou ter sido uma área - fonte de menor importância quando do desenvolvimento da paleobacia; ou por estar inserido parcialmente em um nível crustal inferior durante o metamorfismo. A Formação Arroio dos Nobres. aflorante nos vales Boici e Apati, possivelmente apresenta i dade mais recente que o Grupo Bom Jardim, mas não está inserida no contexto tectônico extensivo atribuído ao Grupo Santa Bárbara, podendo representar uma zona transtrativa tardia ativa.Although the Camaquã Basin has been investigated for a long time, there were few studies that addressed its southernmost fragments. Is not very well know , for example, about the relationship between these sedimentary packages and adjacent units as well as the sedimentary prov enance and their tectono - stratigraphic context. For this reason, such fragments have been framed in different stratigraphic units. There is also a lack of knowledge about the paleogeography that determined the possible source areas of sediment during the d evelopment of these packages belonging to the Arroio dos Nobres Formation. This work aims to analyze depositional models and tectono - sedimentary events in the southern portion of the Camaquã Basin and their contact with the Porongos Complex. The investigat ion addressed to the fragments of the basins of the Apati and Boici valleys will be conducted in terms of faciological analysis, sedimentary origin, structural relationship and bibliographic data review in order to propose a depositional model and stratigr aphic framework for the Arroio dos Nobres Formation in the region of Pinheiro Machado (RS) . For the development of this investigative program, systematic surveys of columnar profiles and respective facies analysis were carried out in the field, and descrip tion compositional and granulometric of clasts, as well as structural analysis, also done by means of satellite images. In the laboratory, heavy minerals were analyzed using scanning electron microscopy. From the application of these methods, it is conclud ed that the study fragments, Apati and Boici, are composed of 28 sedimentary facies grouped into five associations of facies representative of turbiditic fans. As for the stratigraphic framework and structural relationship, the studied sedimentary packages correspond to the Arroio dos Nobres Formation and are in contact with the Porongos Complex through transcurrent faults denoted by outcrops of cataclasites. The provenance study demonstrates that the sediments that filled the Arroio Boici basin and the Apa ti fragment are predominantly from granitic rocks of the Pelotas Terrane . The absence of volcanic clasts indicates that, at the time of formation of these packages, the Pelotas Terrane had its deep crustal level exposed and the volcanic rocks had already b een eroded. There is also a less significant contribution from metamorphic clasts, possibly derived from the Tijucas Terrane (Porongos Complex). This was due to the fact that the Porongos Complex or was a source area of less importance when the developme nt of the paleobasin; or because it is partially inserted in a lower crustal level during metamorphism. The Arroio dos Nobres Formation outcropping in the Boici and Apati valleys, possibly has a more recent age than the Bom Jardim Group, but is not inserte d in the extensive tectonic context attributed to the Santa Bárbara Group, and may represent an active late transt ensional zone

Cultural-clinical psychology: An introduction

Bruna Fujimoto, 49 years old, the daughter of Japanese immigrants who arrived in Brazil in the late 1950s, grew up in a small town with a sizable Japanese minority, where she worked as a receptionist. She married a Brazilian of Italian origin at age 19 in order to please her parents, who wished for her to stay close to home. However, not marrying a Japanese and never having children disappointed her parents. In her early 40s she got divorced and has moved to Rio de Janeiro five years ago, where she says she is “catching up on lost time”. Ms. Fujimoto presents symptoms of fatigue, irritability, low appetite, and social withdrawal. She attributes her symptoms to worries about securing steady employment, lack of a support network in Rio de Janeiro, and guilt about her ailing mother who’s alone after her father’s recent death. As well, she has been facing difficulties in finding a stable romantic partner, expressing concern that her age and her ethnicity (“in between Japanese and Brazilian”) is making it difficult for her to find a match. She finds that she is increasingly keeping to herself and reports mounting anxiety over the past few weeks, particularly about her way of gazing at and being with others, which has become reserved (isolated)

Perceptions of Support Networks During the Graduate Assistant Athletic Trainer Experience

Context: The graduate-assistant position can be a highly influential experience because it is often the first time novice athletic trainers (ATs) are practicing autonomously. Objective: To gain an understanding of how graduate-assistant ATs (GAATs) perceive professional socialization and mentorship during their assistantships. Design: Semistructured phone interviews. Setting: Graduate-assistant ATs in various clinical settings. Patients or Other Participants: Twenty-five GAATs (20 women, 5 men) studying in 1 of 3 academic tracks (postprofessional athletic training = 8, athletic training-based curriculum = 11, non-athletic training-based curriculum = 6). Median age was 24 years. Data Collection and Analysis: Phone interviews were digitally recorded and transcribed verbatim. Data analysis used principles of the general inductive approach. Credibility was maintained using peer review, field notes, and intercoder reliability. Results: Participants identified peer support throughout their experiences, in both academic and clinical settings. The GAATs frequently relied on other GAATs for support due to shared experiences and understanding of workloads. Participants described difficulty receiving supervisor support from fulltime staff ATs due to the supervisors\u27 workload and time constraints, limiting their availability for mentoring. Guidance from academic support personnel occurred only in athletic training-centered academic programs. Communication emerged as helpful for incoming GAATs; the previous GAATs provided formal mentorship via job descriptions highlighting role responsibilities and expectations. Differences between assistantship types were noted only in terms of receiving balanced mentorship between the academic and clinical staffs, such that students studying in postprofessional athletic training programs perceived more balanced support. Conclusions: Our results confirm the literature regarding the GAAT\u27s pursuit of continued formal mentoring. The GAATs perceived less support from full-time AT staff members due to limited availability. Therefore, GAATs leaned on their peers for support during the graduate experience

Coating of Quantum Dots strongly defines their effect on lysosomal health and autophagy

In the last decade the interest in autophagy got an incredible boost and the phenomenon quickly turned into an extensive research field. Interestingly, dysfunction of this cytoplasmic clearance system has been proposed to lie at the root of multiple diseases including cancer. We therefore consider it crucial from a toxicological point of view to investigate if nanomaterials that are developed for biomedical applications interfere with this cellular process. Here, we study the highly promising 'gradient alloyed' Quantum Dots (QDs) that differ from conventional ones by their gradient core composition which allows for better fluorescent properties. We carefully examined the toxicity of two identical gradient alloyed QDs, differing only in their surface coatings, namely 3-mercaptopropionic (MPA) acid and polyethylene glycol (PEG). Next to more conventional toxicological endpoints like cytotoxicity and oxidative stress, we examined the influence of these QDs on the autophagy pathway. Our study shows that the cellular effects induced by QDs on HeLa cells were strongly dictated by the surface coat of the otherwise identical particles. MPA-coated QDs proved to be highly biocompatible as a result of lysosomal activation and ROS reduction, two cellular responses that help the cell to cope with nanomaterial-induced stress. In contrast, PEGylated QDs were significantly more toxic due to increased ROS production and lysosomal impairment. This impairment next results in autophagy dysfunction which likely adds to their toxic effects. Taken together, our study shows that coating QDs with MPA is a better strategy than PEGylation for long term cell tracking with minimal cytotoxicity.status: publishe

Dendrimers as anti-inflammatory agents

Dendrimers constitute an intriguing class of macromolecules which find applications in a variety of areas including biology. These hyperbranched macromolecules with tailored backbone and surface groups have been extensively investigated as nanocarriers for gene and drug delivery, by molecular encapsulation or covalent conjugation. Dendrimers have provided an excellent platform to develop multivalent and multifunctional nanoconjugates incorporating a variety of functional groups including drugs which are known to be anti-inflammatory agents. Recently, dendrimers have been shown to possess anti-inflammatory properties themselves. This unexpected and intriguing discovery has provided an additional impetus in designing novel active pharmaceutical agents. In this review, we highlight some of the recent developments in the field of dendrimers as nanoscale anti-inflammatory agents